摘要
目的分析儿童活体肝移植中供受体CYP3A5基因多态性及其与患儿肝移植术后他克莫司浓度／剂量比的关系，为肝移植术后他克莫司的个体化用药提供可靠的参考指标，优化用药方案并减少不良反应。方法收集本治疗组活体肝移植中供受体外周血标本，使用PCR-SSP法测定CYP3A5基因型，收集患儿术后他克莫司用药剂量以及血药浓度相关数据。根据受体基因型可将所有患儿分为受体表达组和受体非表达组，根据供体基因型可将所有患儿分为供体表达组和供体非表达组，根据供受体基因型分为3组：即供体非表达／受体非表达组、供体／受体单一表达组、供体表达／受体表达组，分别进行统计分析。结果78例供受体中CYP3A5＊3＊347例（60．3oA），CYP3A5＊1＊328例（35．9％），CYP3A5＊1＊13例（3．8％）。受体基因表达组比受体基因非表达组术后1、2、4、8周C0／D明显更低，差异有统计学意义（P〈0．05）；供体基因表达组比供体基因非表达组受体术后1、2、4周C0／D明显更低，差异有统计学意义（P〈0．05）；供体非表达／受体非表达组术后第1、2、4、8周C0／D显著高于供体／受体单一表达组及供体表达／受体表达组，差异有统计学意义（P〈0．05）；供体／受体单一表达组与供体表达／受体表达组相比术后1、2、4、8周C0／D差异均无统计学意义（P〉0．05）。结论供受体CYP3A5基因多态性与肝移植术后早期受体的他克莫司用药剂量及所达到的全血谷值浓度的个体化差异密切相关，在儿童活体肝移植中需要同时考虑供受体基因对受体术后他克莫司药代动力学的影响，要达到相同的血药浓度，供体／受体基因型中只要其中一方含有CYP3A5＊1等位基因，术后所需的他克莫司剂量就会相应增加。分析供受体CYP3A5基因多态性可以为肝移植术后他克莫司的个体化用药提供可靠的参考指标，指导最佳的用药剂量，提高药效并减少不良反应。
Objective To analyze CYP3A5 gene of living donor liver transplantation and examine polymorphism of donor and recipient in children the tacrolimus concentration/dose ratio after transplantation to provide reliable reference rationales for using tacrolimus after transplantation, optimize drug regimens and reduce adverse reactions. Methods Blood samples were collected from donor and living donor liver transplant in our treatment group. And the CYP3A5 genotypes were determined by polymerase chain reaction-sequence specific primer （PCR-SSP）. The concentration/dose ratio was recorded after transplantation. According to the genotype of recipient, they were divided into recipient expression and non-expression groups; According to the genotype of donor, donor expression and non-expression groups; According to the genotype of donor and recipient, donor non-expression/ recipient non-expression, donor or recipient expression and donor expression/recipient expression. Results The CYP3A5 genotypes of 78 patients were composed of 47 CYP3A5 ＊ 3 ＊ 3 （60. 3%）, 28 CYP3A5＊ 1 ＊ 3 （35.9%） and 3 CYP3A5 -1 ＊ 1 （3. 8%）. The G0/D of recipient expression group was significantly lower than that of recipient non-expression group at Week 1, 2, 4 and 8 post-transplantation. The CO/D of donor expression group was significantly lower than donor non-expression group at Week 1, 2 and 4 post-transplantation. The CO/D of donor non-expression/ recipient non-expression group was significantly lower than donor or recipient expression group at Week 1, 2, 4 and 8 post-transplantation. However, no significant difference existed between the C0/ D of donor or recipient expression group and the C0/D of the donor expression/recipient expression group at Week 1, 2, 4 and 8 post-transplantation. Conclusions CYP3A5 gene polymorphism is highly correlated with individual differences in the doses of tacrolimus and blood trough concentrations after transplantation. The CYP3A5 genotypes of donor and recipient have the same effect on CO/D ratio after living donor liver transplantation.
出处
《中华小儿外科杂志》
CSCD
北大核心
2014年第6期452-456,共5页
Chinese Journal of Pediatric Surgery
